Lipid induced alteration in retinoic acid signaling leads to mitochondrial dysfunction in HepG2 and Huh7 cells

Biochem Cell Biol. 2023 Feb 14. doi: 10.1139/bcb-2022-0266. Online ahead of print.ABSTRACTA surfeit of mitochondrial ROS and inflammation serve as obligatory mediators of lipid-associated hepatocellular maladies. While retinoid homeostasis is essential in restoring systemic energy balance, its role in hepatic mitochondrial function remains elusive. The role of Lecithin: Retinol Acyl Transferase (LRAT) in maintenance of retinoid homeostasis is appreciated earlier, however its role in modulating retinoic acid (RA) bioavailability upon lipid-imposition is unexplored. We identified LRAT overexpression in HFD-fed rats and palmitate-treated hepatoma cells. Elevation in LRAT expression depletes RA production and deregulates RA signaling. This altered RA metabolism enhances fat accumulation, accompanied by inflammation that leads to impaired mitochondrial function through enhanced ROS generation. Hence, LRAT inhibition could be a novel approach preventing lipid-induced mitochondrial dysfunction in hepatoma cells.PMID:36787544 | DOI:10.1139/bcb-2022-0266

Source: Biochemistry and Cell Biology - February 14, 2023 Category: Biochemistry Authors: Eshani Karmakar Nabanita Das Bidisha Mukherjee Prosenjit Das Satinath Mukhopadhyay Sib Sankar Roy Source Type: research